Identification of a novel aspartic-like protease differentially expressed in human breast cancer cell lines

four different human breast cancer cell lines were examined to search for g enes associated with tumor growth and metastasis. Each of these cell lines, MDA-MB-453, MCF-7, MDA-MB-231 and MDA-MB-435, displays different phenotypi c characteristics ranging from poorly to highly tumorigenic and metastatic. The differences in gene expression profiles of these cell lines generated by differential display technique should allow one to identify candidates a s putative oncogenes or tumor/metastasis suppressor genes. A novel cDNA exp ressed in the highly tumorigenic and metastatic cell line, MDA-MB-435, was identified and isolated by this approach. The function for this gene, desig nated ALP56 (aspartic-like protease 56 kDa), in tumor progression is sugges ted by the homology of the encoded protein to aspartic proteases, such as c athepsin D. The amino acid residues in two catalytic domains of this family are highly conserved in those domains of ALP56, Northern hybridization ind icated that the expression of ALP56 is associated with growth and metastasi s of MDA-MB-435 tumors in immunodeficient mice. In situ hybridization of bi opsies from breast cancer and colon cancer patients indicated that ALP56 is upregulated in human primary tumors and liver metastasis. These results su ggest that this novel gene correlates with human tumor progression. (C) 200 0 Elsevier Science B.V. All rights reserved.